Department of Vascular Surgery, Huai'an First People's Hospital Affiliated to Nanjing Medical University, Huai'an, Jiangsu, China.
Department of Gastrointestinal Surgery, Huai'an First People's Hospital Affiliated to Nanjing Medical University, Huai'an, Jiangsu, China.
Biomed Res Int. 2021 Jan 9;2021:8889986. doi: 10.1155/2021/8889986. eCollection 2021.
The epithelial-mesenchymal transition (EMT) is a key hallmark of cancer which promotes malignant progression, especially during the process of cancer invasion. A better understanding of EMT will help elucidate the molecular mechanism underlying colorectal cancer (CRC) metastasis and may provide new insights into the identification of potential biomarkers and therapeutic targets.
A series of bioinformatic approaches were combined and identify GLI3 as a potential key regulator in EMT. In vitro experiments were performed to knockdown GLI3 expression in two CRC cell lines and to reveal the oncogenic role of GLI3 in CRC. qRT-PCR and western blot were performed to show the influence of GLI3 in EMT and downstream pathways. The Kaplan-Meier analysis and log-rank test were used to evaluate the prognostic value of GLI3 in CRC patients.
GLI3 was identified as a key regulator in coexpression and protein-protein interaction (PPI) networks involved in EMT. Bioinformatic analyses indicated that GLI3 had a high correlation with EMT markers in CRC. In vitro experiments showed that GLI3 knockdown attenuated the migratory and invasive capacities of CRC cells via influencing EMT property, especially by regulating phosphorylation of ERK signaling pathway. In addition, higher expression of GLI3 predicts worse prognosis in CRC patients.
In summary, we presented the first evidence that GLI3 could promote the migratory and invasive capacities of CRC cells by regulating the EMT process. Our study might provide some useful clues to a better understanding of GLI3 in EMT during CRC progression.
上皮-间质转化（EMT）是癌症的一个关键标志，促进恶性进展，特别是在癌症侵袭过程中。更好地了解 EMT 将有助于阐明结直肠癌（CRC）转移的分子机制，并可能为识别潜在的生物标志物和治疗靶点提供新的见解。
采用一系列生物信息学方法，确定 GLI3 是 EMT 中的一个潜在关键调节因子。在体外实验中，在两种 CRC 细胞系中敲低 GLI3 的表达，以揭示 GLI3 在 CRC 中的致癌作用。qRT-PCR 和 Western blot 用于显示 GLI3 在 EMT 和下游通路中的影响。Kaplan-Meier 分析和对数秩检验用于评估 GLI3 在 CRC 患者中的预后价值。
GLI3 被确定为 EMT 相关共表达和蛋白质-蛋白质相互作用（PPI）网络中的关键调节因子。生物信息学分析表明，GLI3 与 CRC 中的 EMT 标志物具有高度相关性。体外实验表明，GLI3 敲低通过影响 EMT 特性，特别是通过调节 ERK 信号通路的磷酸化，减弱 CRC 细胞的迁移和侵袭能力。此外，GLI3 表达水平越高，CRC 患者的预后越差。
综上所述，我们首次提出证据表明，GLI3 可以通过调节 EMT 过程促进 CRC 细胞的迁移和侵袭能力。我们的研究可能为更好地理解 CRC 进展过程中的 GLI3 在 EMT 中的作用提供一些有用的线索。
